Kinase Subfamily FAM20A
FAM20AC is a subfamily of the Four-Jointed family of secretory kinases. It consists of two genes (FAM20A and FAM20C) in humans and all other vertebrates, and one or more homologs in other deuterostomes, in insects and in nematodes.
Phylogeny Notes
FAM20A is single copy in all vertebrates, but FAM20C is dynamic: it appears to be duplicated four-fold in most fish, though lost from some, and an additional likely paralog is found from amphibians to platypus, but not in placental mammals or fish. A single FAM20AC-like gene is found in some invertebrate chordates (Branchiostoma and Saccoglossus) but it is apparently lost from Ciona. Urchins have two FAM20AC genes, one similar to the invertebrate chordates, and the other highly divergent. Insects and nematodes also have just one copy.
Functions
Mutations in FAM20C were found to cause bone disorders (Raine Syndrome / Lethal Osteosclerotic Bone Dysplasia) giving rise to abnormally hard and dense bone, usually lethal within hours of birth. Four different non-synonymous changes at 3 positions were found, along with several splice site mutations and a deletion. The disorder is recessive, and while the mutant residues are conserved within vertebrates, they are not conserved within the whole family and do not effect the catalytic residues. Mouse FAM20C (aka DMP4) is selectively expressed in mineralizing bone, and in developing teeth, the differentiation of that odontoblasts, the dentin (mineral)-secreting cells is modulated by FAM20C levels [1]
http://en.wikipedia.org/wiki/Odontoblast
References
- Hao J, Narayanan K, Muni T, Ramachandran A, and George A. Dentin matrix protein 4, a novel secretory calcium-binding protein that modulates odontoblast differentiation. J Biol Chem. 2007 May 25;282(21):15357-65. DOI:10.1074/jbc.M701547200 |
- Simpson MA, Hsu R, Keir LS, Hao J, Sivapalan G, Ernst LM, Zackai EH, Al-Gazali LI, Hulskamp G, Kingston HM, Prescott TE, Ion A, Patton MA, Murday V, George A, and Crosby AH. Mutations in FAM20C are associated with lethal osteosclerotic bone dysplasia (Raine syndrome), highlighting a crucial molecule in bone development. Am J Hum Genet. 2007 Nov;81(5):906-12. DOI:10.1086/522240 |
